Alpha-nor-d-homosteroids



United States Patent 3,387,023 A-VOR-D-HOMOSTEROIDS Seymour D. Levine, North Brunswick, N.J., assignor to E. R. Squibb & Sons, Inc., New York, N.Y., a corporation of Delaware No Drawing. Filed Mar. 17,1966, Ser. No. 535,055 5 Claims. (Cl. 260-488) This invention rel-ates to and has as its object the provision of new physiologically active steroids, processes for their production and novel intermediates useful in the preparation thereof.

More particularly, this invention relates to A-nor-D- homosteroids having the formula CH3 on wherein R is selected from the group consisting of hydrogen and acyl.

The preferred acyl radicals are those of hydrocarbon carboxylic acids of less than twelve carbon atoms, as exemplified by the lower alkanoic acids (e.g., acetic, propionic, butyn'c and tert-pentanoic acid), the lower 'alkenoic acids, the monocyclic aryl carboxylic acids (e.g., benzoic and toluic acid), the monocyclic aryl lower alkanoic acids (e.g., phenacetic and fi-phenylpropionic acid), the cycloalkane carboxylic acids and the cycloalkene carboxylic acids.

The novel compounds of this invention are pharmacologically active substances which possess anti-androgenic activity (i.e., they inhibit the actions of androgens), and which may be used in the treatment of such conditions as hyperandrogenic acne.

The compounds may be formulated for such administration, and concentration and/ or dosage being based on the activity of the particular compound and the requirements of the patient.

The compounds of this invention may be prepared according to the processes of this invention beginning with 17a-hydroxy-A-norprogesterone. This starting material may be prepared by the process disclosed in copending US. patent application, Ser. No. 399,838, filed Sept. 28, 1964.

It has been discovered that when 17a-hYdIOXY-A- norprogesterone is treated with an alcoholic solution of potassium hydroxide the 17-aa-methy1-17aB-ol and the 17afl-1nethyl-17aa-o1 compounds of this invention are obtained.

These compounds may be acylated by treating the hydroxy compound with the requisite acid anhydride in the presence of perchloric acid.

The following examples illustrate this invention; all temperatures are in degrees centigrade unless otherwise stated:

Example 1.-17aa-methyl-A -A-nor-D-homoandrostene- 2, 17 -dione-17a 8-ol; 17a/3-rnethyLA -A-nor D homoandrostene-Z,17-dione-17aa-ol "ice A solution of 500 mg. of 17a-hydroxy-A-norprogesterone in 300 ml. of ethanol and 300 ml. of 10% potassium hydroxide solution is refluxed for five hours and then extracted with ethyl acetate. The ethyl acetate extracts are washed with 8% salt solution, dried (sodium sulfate) and evaporated to dryness. The residue is a mixture of the title compounds which can be separated by plate chromatography using neutral alumina (Activity V) as the adsorbent and chloroform as the developing solvent.

Example 2.--17aa-methyl-A -A-nor-D-homoandrostene-Z, 17-dion-e- 1 7aB-acetate Utilizing 17aa-methyl-A -A-nor-D-homoandrostene-2, 17-dione-17a 3-ol and treating it with acetic anhydride in the presence of perchloric acid, the product formed is 17am methyl A A nor D homoandrostene 2, 17-dione-17a/3-acetate.

Example 3.-17a 3-methyl-A -A-n0r-D-homoandrostene-2,

17 -d-ione-17aa-ol 17-acetate Utilizing 17am-methyl-M-A-nor-D-homoandrostene-2, 17-dione-17aa-ol and treating it with acetic anhydride in the presence of perchloric acid, the product formed is 17afl methyl A nor D homoandrostane 2,17 dione-17aa-ol.

The invention may be variously otherwise embodied within the scope of the appended claims.

What is claimed is:

1. A compound having the formula CH 0R References Cited UNITED STATES PATENTS 3/1962 Amiard et a1. 260-476 7/1965 Reimann et a1. 260488 LORRAINE A. WEINBERGER, Primary Examiner.

VIVIAN GARNER, Assistant Examiner. 

1. A COMPOUND HAVING THE FORMULA 